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Q15031 (SYLM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Probable leucine--tRNA ligase, mitochondrial

EC=6.1.1.4
Alternative name(s):
Leucyl-tRNA synthetase
Short name=LeuRS
Gene names
Name:LARS2
Synonyms:KIAA0028
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length903 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Catalytic activity

ATP + L-leucine + tRNA(Leu) = AMP + diphosphate + L-leucyl-tRNA(Leu).

Subcellular location

Mitochondrion matrix By similarity.

Tissue specificity

Ubiquitously expressed, but highest expression in tissues with high metabolic rates, such as skeletal muscle, heart, and kidney. Ref.4

Involvement in disease

Perrault syndrome 4 (PRLTS4) [MIM:615300]: A sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6

Sequence similarities

Belongs to the class-I aminoacyl-tRNA synthetase family.

Sequence caution

The sequence BAA04877.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – ?Mitochondrion Potential
Chain? – 903Probable leucine--tRNA ligase, mitochondrialPRO_0000035806

Regions

Motif92 – 10211"HIGH" region
Motif639 – 6435"KMSKS" region

Sites

Binding site6421ATP By similarity

Amino acid modifications

Modified residue681N6-acetyllysine By similarity
Modified residue2361N6-acetyllysine Ref.3

Natural variations

Natural variant5221T → N in PRLTS4; reduced activity. Ref.6
VAR_070094
Natural variant6291T → M in PRLTS4; found in a compound heterozygote also carrying a null mutation; the mutant is functional in a yeast complementaion assay but might be insufficient as a heterozygote with a fully non-functional allele. Ref.6
VAR_070095
Natural variant7271K → N.
Corresponds to variant rs36054230 [ dbSNP | Ensembl ].
VAR_052638
Natural variant8311E → D.
Corresponds to variant rs9827689 [ dbSNP | Ensembl ].
VAR_052639

Sequences

Sequence LengthMass (Da)Tools
Q15031 [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: D9AC143125124F58

FASTA903101,976
        10         20         30         40         50         60 
MASVWQRLGF YASLLKRQLN GGPDVIKWER RVIPGCTRSI YSATGKWTKE YTLQTRKDVE 

        70         80         90        100        110        120 
KWWHQRIKEQ ASKISEADKS KPKFYVLSMF PYPSGKLHMG HVRVYTISDT IARFQKMRGM 

       130        140        150        160        170        180 
QVINPMGWDA FGLPAENAAV ERNLHPQSWT QSNIKHMRKQ LDRLGLCFSW DREITTCLPD 

       190        200        210        220        230        240 
YYKWTQYLFI KLYEAGLAYQ KEALVNWDPV DQTVLANEQV DEHGCSWRSG AKVEQKYLRQ 

       250        260        270        280        290        300 
WFIKTTAYAK AMQDALADLP EWYGIKGMQA HWIGDCVGCH LDFTLKVHGQ ATGEKLTAYT 

       310        320        330        340        350        360 
ATPEAIYGTS HVAISPSHRL LHGHSSLKEA LRMALVPGKD CLTPVMAVNM LTQQEVPVVI 

       370        380        390        400        410        420 
LAKADLEGSL DSKIGIPSTS SEDTILAQTL GLAYSEVIET LPDGTERLSS SAEFTGMTRQ 

       430        440        450        460        470        480 
DAFLALTQKA RGKRVGGDVT SDKLKDWLIS RQRYWGTPIP IVHCPVCGPT PVPLEDLPVT 

       490        500        510        520        530        540 
LPNIASFTGK GGPPLAMASE WVNCSCPRCK GAAKRETDTM DTFVDSAWYY FRYTDPHNPH 

       550        560        570        580        590        600 
SPFNTAVADY WMPVDLYIGG KEHAVMHLFY ARFFSHFCHD QKMVKHREPF HKLLAQGLIK 

       610        620        630        640        650        660 
GQTFRLPSGQ YLQREEVDLT GSVPVHAKTK EKLEVTWEKM SKSKHNGVDP EEVVEQYGID 

       670        680        690        700        710        720 
TIRLYILFAA PPEKDILWDV KTDALPGVLR WQQRLWTLTT RFIEARASGK SPQPQLLSNK 

       730        740        750        760        770        780 
EKAEARKLWE YKNSVISQVT THFTEDFSLN SAISQLMGLS NALSQASQSV ILHSPEFEDA 

       790        800        810        820        830        840 
LCALMVMAAP LAPHVTSEIW AGLALVPRKL CAHYTWDASV LLQAWPAVDP EFLQQPEVVQ 

       850        860        870        880        890        900 
MAVLINNKAC GKIPVPQQVA RDQDKVHEFV LQSELGVRLL QGRSIKKSFL SPRTALINFL 


VQD 

« Hide

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1."
Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.
DNA Res. 1:27-35(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Bone marrow.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[3]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-236, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[4]"Human mitochondrial leucyl-tRNA synthetase corrects mitochondrial dysfunctions due to the tRNALeu(UUR) A3243G mutation, associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like symptoms and diabetes."
Li R., Guan M.X.
Mol. Cell. Biol. 30:2147-2154(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[5]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome."
Pierce S.B., Gersak K., Michaelson-Cohen R., Walsh T., Lee M.K., Malach D., Klevit R.E., King M.C., Levy-Lahad E.
Am. J. Hum. Genet. 92:614-620(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PRLTS4 ASN-522 AND MET-629, CHARACTERIZATION OF VARIANTS PRLTS4 ASN-522 AND MET-629.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D21851 mRNA. Translation: BAA04877.2. Different initiation.
BC025989 mRNA. Translation: AAH25989.1.
RefSeqNP_056155.1. NM_015340.3.
XP_005265063.1. XM_005265006.1.
UniGeneHs.526975.

3D structure databases

ProteinModelPortalQ15031.
SMRQ15031. Positions 53-901.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116968. 3 interactions.
STRING9606.ENSP00000265537.

Chemistry

DrugBankDB00149. L-Leucine.

PTM databases

PhosphoSiteQ15031.

Polymorphism databases

DMDM2501029.

Proteomic databases

PaxDbQ15031.
PeptideAtlasQ15031.
PRIDEQ15031.

Protocols and materials databases

DNASU23395.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265537; ENSP00000265537; ENSG00000011376.
ENST00000415258; ENSP00000408576; ENSG00000011376.
GeneID23395.
KEGGhsa:23395.
UCSCuc003cop.1. human.

Organism-specific databases

CTD23395.
GeneCardsGC03P045405.
HGNCHGNC:17095. LARS2.
HPAHPA035951.
HPA045450.
MIM604544. gene.
615300. phenotype.
neXtProtNX_Q15031.
Orphanet2855. Perrault syndrome.
PharmGKBPA134982982.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0495.
HOGENOMHOG000200747.
HOVERGENHBG017877.
InParanoidQ15031.
KOK01869.
OMAGIEHACM.
OrthoDBEOG754HNN.
PhylomeDBQ15031.
TreeFamTF105662.

Enzyme and pathway databases

BRENDA6.1.1.4. 2681.
ReactomeREACT_71. Gene Expression.
SABIO-RKQ15031.

Gene expression databases

ArrayExpressQ15031.
BgeeQ15031.
CleanExHS_LARS2.
GenevestigatorQ15031.

Family and domain databases

Gene3D1.10.730.10. 1 hit.
3.40.50.620. 3 hits.
3.90.740.10. 1 hit.
InterProIPR001412. aa-tRNA-synth_I_CS.
IPR002300. aa-tRNA-synth_Ia.
IPR002302. Leu-tRNA-ligase_bac/mito.
IPR014729. Rossmann-like_a/b/a_fold.
IPR009080. tRNAsynth_1a_anticodon-bd.
IPR013155. V/L/I-tRNA-synth_anticodon-bd.
IPR009008. Val/Leu/Ile-tRNA-synth_edit.
[Graphical view]
PANTHERPTHR11946:SF7. PTHR11946:SF7. 1 hit.
PfamPF08264. Anticodon_1. 1 hit.
PF00133. tRNA-synt_1. 3 hits.
[Graphical view]
PRINTSPR00985. TRNASYNTHLEU.
SUPFAMSSF47323. SSF47323. 1 hit.
SSF50677. SSF50677. 1 hit.
TIGRFAMsTIGR00396. leuS_bact. 1 hit.
PROSITEPS00178. AA_TRNA_LIGASE_I. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiLARS2.
GenomeRNAi23395.
NextBio45533.
PROQ15031.
SOURCESearch...

Entry information

Entry nameSYLM_HUMAN
AccessionPrimary (citable) accession number: Q15031
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: April 16, 2014
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Aminoacyl-tRNA synthetases

List of aminoacyl-tRNA synthetase entries